Davide Trotti, PhD

Amyotrophic Lateral Sclerosis, Neurodegenerative diseases, Glutamate transporters and excitotoxicity, mitochondria ion channels and apoptosis

Research in my laboratory within the Weinberg Unit for ALS Research is focused on the study of molecular mechanisms of excitotoxicity leading to motor neuron degeneration in amyotrophic lateral sclerosis (ALS). ALS is the most common adult motor neuron disease and its primary hallmark is the death of motor neurons of the spinal cord which leads to spasticity, hyper-reflexia, general weakness and muscle atrophy. Failure of respiratory muscles is generally the fatal event, occurring within 1-5 years of symptoms onset. Impairment in the glutamate transport system and loss of the glutamate transporter EAAT2 (a.k.a. GLT-1) are pathological events contributing to motor neuron death in ALS. We have accumulated expertise in the study of molecular mechanisms regulating the activity of glutamate transporters, their expression levels and post-translational modifications.

Another objective of our research is the study of mitochondria and the molecular mechanisms leading to their impaired physiology in ALS. Mitochondria are one of the main sources of energy production for the cells and play a pivotal role in maintaining neuronal cell alive. A pathology-driven impairment in these organelles may shift the balance between life and death and lead to neuronal degeneration.

We use a variety of biochemical, cellular and molecular biology techniques applied to primary cultures of astrocytes and motor neurons, embryonic stem cell-derived motor neurons and organotypic cultures isolated from transgenic mice and rats model of ALS. We also use electrophysiological techniques such as patch clamp, to study ionic conductances of the outer and inner membrane of mitochondria isolated from the spinal cord of transgenic mice model of ALS, and two-electrode voltage clamp to study the function of glutamate transporters expressed in cell lines and oocytes harvested from Xenopus laevis frogs.

The ultimate goal of our research is to unravel the molecular mechanisms of neurodegeneration in ALS and identify potential therapeutic targets that can be used in drug screening platforms for treating ALS.

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